Chimerism after bone marrow transplantation (BMT) can be either complete, where the marrow and the peripheral lympho/hematopoietic cells are all of donor origin, or mixed, where the lympho/hematopoietic cells are a mixture of donor and host origin. In this application we are proposing to continue our study of mixed hematopoietic chimerism using DNA probes. The work will focus on three goals including: (1) The correlation of mixed hematopoietic chimerism with the type of disease and the incidence of GVHD and recurrent malignancy. (2) To develop additional DNA probes to facilitate the study of chimerism as well as to improve the sensitivity of detection. (3) To further characterize the phenomenon and to direct future studies on it's mechanism we propose to study the kinetics of development of mixed hematopoietic chimerism and investigate the cell lineage(s) involved. HLA differences between donor and recipients lead to graft- versus-host disease (GVHD). Patients transplanted for various hematological malignancies at the City of Hope Bone Marrow Transplant Unit have all been transplanted with marrow from HLA-A, B, C, and DR identical siblings. Furthermore, the donor and recipient cells are determined by the mixed lymphocyte culture reaction (MLR) to be HLA-D compatible. Although this type of matching insures maximal graft survival, it does not eliminate GVHD. The mechanism that triggers this cell-mediated phenomenon is still not elucidated. It is highly likely that some individuals possess genomic DNA differences within the HLA-D region that are not detected at the serological level. The degree to which class II gene mismatch occurs in serologically HLA identical siblings is not well characterized. Furthermore, the influence of this molecular HLA non-identity on graft survival and GVHD has not been studied in detail. It is the goal of this study to determine the degree and type of molecular HLA non-identity between recipients and donors and to correlate these observations on the clinical outcome of the graft, especially the degree of GVHD and the incidence of mixed hematopoietic chimerism observed.